TScan Therapeutics uncloaks with $48M to unleash new TCR targets

Boston skyline from harbor
TScan Therapeutics is built upon the work of Stephen Elledge, Ph.D., a professor of genetics and medicine at Harvard Medical School. (usmc0491/Pixabay)

TScan Therapeutics launched Wednesday with $48 million, a star-studded management team and T-cell receptor (TCR) technology out of Harvard University. The company aims to uncover new targets for T-cell therapies and bring them to more patients with both solid tumors and blood cancers. 

CEO David Southwell, the former Human Genome Sciences chief financial officer who went on to helm Inotek Pharma through its merger with Rocket Pharma, is running TScan alongside Merrimack alum Gavin MacBeath as chief scientific officer, Amgen veteran and Chief Business Officer Henry Rath and CFO Robert Crane, who’s been with the company since the beginning. 

Founded in April 2018, TScan is built upon the work of Stephen Elledge, Ph.D., a professor of genetics and medicine at Harvard Medical School. 

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“He’s been working on this platform for seven years or so … What he wanted to do—and what our objective is—was to open up the field of immunotherapy by finding undiscovered, common intracellular targets,” Southwell told FierceBiotech. “There are probably 10 or so targets that have been discovered inside the cell, but we think there are many, many more. I think everyone would agree on that. Unlike other companies, we are entirely focused on finding them.” 

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The technology is a genomewide, high-throughput system designed to discover the natural targets of TCRs, the company said. It’s particularly interested in finding new antigens across different patients and cancer types and matching them with TCRs that target them. But that’s not all—the platform can also discover unintended side effects of binding T cells to these antigens. 

“We can also discover off-target effects, which is really important because in one of the first clinical trials done in TCR, patients were given an anti-MAGE-A3 TCR and both died of heart attacks,” Southwell said. It turned out that the TCR was “very active” against a receptor on heart cells as well as on MAGE-A3 found in cancer cells. TScan wants to figure out these side effects before treatments even get into patients. 

"We've got a library of cancer antigens, but also a library that covers the whole human peptidome of antigens,” Southwell said. “We start by taking a TCR and finding the cancer antigen it is effective against. Say we’ve found a TCR that will kill an antigen, then we need to test it to see if it has off-target effects. We would run it against another library to see if we have those.”  

Southwell stressed that TScan is using a biologic approach rather than the predictive one used by machine-learning-based drug discovery companies. 

The Cambridge, Massachusetts-based company wants to go after both solid tumors and blood cancers that tend not to respond well to immunotherapy, such as acute myeloid leukemia. It intends to take some programs forward on its own but plans to license some out as well. 

“The platform is way more powerful than we could properly execute on our own. We kind of need pharma partners to properly take full advantage of the platform,” Southwell said. 

And there could be plenty of interest on the pharma side, if Novartis—maker of the chimeric antigen receptor T-cell therapy Kymriah—investing in TScan’s series B round is any indication. 

Both Novartis Venture Fund and Novartis Institutes for BioMedical Research are backing TScan, as are its founding investor Longwood Fund, Bessemer Venture Partners and Alphabet’s venture arm GV.

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